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A Systematic Review of Animal Models of Disuse-Induced Bone Loss

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Abstract

Objective

Several different animal models are used to study disuse-induced bone loss. This systematic review aims to give a comprehensive overview of the animal models of disuse-induced bone loss and provide a detailed narrative synthesis of each unique animal model.

Methods

PubMed and Embase were systematically searched for animal models of disuse from inception to November 30, 2019. In addition, Google Scholar and personal file archives were searched for relevant publications not indexed in PubMed or Embase. Two reviewers independently reviewed titles and abstracts for full-text inclusion. Data were extracted using a predefined extraction scheme to ensure standardization.

Results

1964 titles and abstracts were screened of which 653 full-text articles were included. The most common animal species used to model disuse were rats (59%) and mice (30%). Males (53%) where used in the majority of the studies and genetically modified animals accounted for 7%. Twelve different methods to induce disuse were identified. The most frequently used methods were hindlimb unloading (44%), neurectomy (15%), bandages and orthoses (15%), and botulinum toxin (9%). The median time of disuse was 21 days (quartiles: 14 days, 36 days) and the median number of animals per group subjected to disuse was 10 (quartiles: 7, 14). Random group allocation was reported in 43% of the studies. Fewer than 5% of the studies justified the number of animals per group by a sample size calculation to ensure adequate statistical power.

Conclusion

Multiple animal models of disuse-induced bone loss exist, and several species of animals have successfully been studied. The complexity of disuse-induced bone loss warrants rigid research study designs. This systematic review emphasized the need for standardization of animal disuse research and reporting.

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Acknowledgements

We thank research librarian and information specialist Annette Balle Sørensen from Aarhus University for valuable insights and help in developing the search strategy. Jose Luis Ferretti, Neil Fedarko, and Piret Hussar are thanked for providing copies of their research not retrievable elsewhere.

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    Authors and Affiliations

    1. Department of Biomedicine, Aarhus University, Aarhus, Denmark

      Mikkel Bo Brent, Annemarie Brüel & Jesper Skovhus Thomsen

    2. Department of Biomedicine, Health, Aarhus University, Wilhelm Meyers Allé 3, 8000, Aarhus C, Denmark

      Mikkel Bo Brent

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    MBB is the project manager, guarantor, and drafted the manuscript. MBB and JST developed the search and methodological strategy and screened eligible abstracts and full-text articles. MBB, MB, and JST read, provided feedback, and approved the final manuscript.

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    Appendix A

    Appendix A

    Search string for PubMed and Embase.

     

    PubMed

    Embase

    Block 1

    (bone*[tiab] OR skeleton*[tiab])

    (bone*:ab,ti OR skeleton*:ab,ti)

    AND

    Block 2

    (immobilisation*[tiab] OR immobilization*[tiab] OR disuse*[tiab] OR "non ambulating"[tiab] OR restraint*[tiab] OR unloading*[tiab] OR "non weight bearing"[tiab] OR "non load bearing"[tiab] OR "non loadbearing"[tiab] OR paralyzed*[tiab] OR paralysed*[tiab] OR monoplegic*[tiab] OR paraplegic*[tiab] OR hemiplegic*[tiab] OR tetraplegic*[tiab] OR quadroplegic*[tiab])

    (immobilisation*:ab,ti OR immobilization*:ab,ti OR disuse*:ab,ti OR "non ambulating":ab,ti OR restraint*:ab,ti OR unloading*:ab,ti OR "non weight bearing":ab,ti OR "non load bearing":ab,ti OR "non loadbearing":ab,ti OR paralyzed*:ab,ti OR paralysed*:ab,ti OR monoplegic*:ab,ti OR paraplegic*:ab,ti OR hemiplegic*:ab,ti OR tetraplegic*:ab,ti OR quadroplegic*:ab,ti)

    AND

    Block 3

    Search filter for animal experimentation developed by Hooijmans et al. [19]

    Search filter for animal experimentation developed by de Vries et al. [20]

    NOT

    Block 4

    ("letter"[publication type] OR "comment"[publication type] OR "editorial"[publication type] OR review[publication type])

    ('conference abstract'/it OR 'conference paper'/it OR 'conference review'/it OR 'review'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) AND [embase]/lim NOT [medline]/lim

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    Brent, M.B., Brüel, A. & Thomsen, J.S. A Systematic Review of Animal Models of Disuse-Induced Bone Loss. Calcif Tissue Int 108, 561–575 (2021). https://doi.org/10.1007/s00223-020-00799-9

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    • DOI: https://doi.org/10.1007/s00223-020-00799-9

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